ASSISTED VENTILATION

Local activation of coagulation and inhibition of fibrinolysis in the lung during ventilator associated pneumonia

M J Schultz^1,2, J Millo³, M Levi⁴, C E Hack⁵, G J Weverling⁶, C S Garrard³, T van der Poll^2,7

¹ Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
² Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam
³ Intensive Therapy Unit, John Radcliffe Hospital, Oxford, UK
⁴ Department of Internal Medicine, Academic Medical Center, University of Amsterdam
⁵ Department of Pathophysiology of Plasma Proteins, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands
⁶ Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam
⁷ Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam

Correspondence to:
Correspondence to:
Dr M J Schultz
Academic Medical Center, University of Amsterdam, Department of Intensive Care Medicine, C3-329, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; m.j.schultz{at}amc.uva.nl

Background: Fibrin deposition is a hallmark of pneumonia. To determine the kinetics of alterations in local coagulation and fibrinolysis in relation to ventilator associated pneumonia (VAP), a single centre prospective study of serial changes in pulmonary and systemic thrombin generation and fibrinolytic activity was conducted in patients at risk for VAP.

Methods: Non-directed bronchial lavage (NBL) was performed on alternate days in patients expected to require mechanical ventilation for more than 5 days. A total of 28 patients were studied, nine of whom developed VAP.

Results: In patients who developed VAP a significant increase in thrombin generation was observed in the airways, as reflected by a rise in the levels of thrombin-antithrombin complexes in NBL fluid accompanied by increases in soluble tissue factor and factor VIIa concentrations. The diagnosis of VAP was preceded by a decrease in fibrinolytic activity in NBL fluid. Indeed, before VAP was diagnosed clinically, plasminogen activator activity levels in NBL fluid gradually declined, which appeared to be caused by a sharp increase in NBL fluid levels of plasminogen activator inhibitor 1.

Conclusion: VAP is characterised by a shift in the local haemostatic balance to the procoagulant side, which precedes the clinical diagnosis of VAP.

Keywords: ventilator associated pneumonia; coagulation; fibrinolysis; inflammation; cytokines

Abbreviations: NBL, non-directed bronchial lavage; PAA, plasminogen activator activity; PAI-1, plasminogen activator inhibitor type 1; TATc, thrombin-antithrombin complexes; TF, tissue factor; t-PA, tissue type plasminogen activator; u-PA, urokinase type plasminogen activator; VAP, ventilator associated pneumonia

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